A mentored, patient-oriented, research project is proposed to provide the candidate with rigorous training and experience in studying the virologic effects of human papillomavirus (HPV) vaccine introduction. The impact of the new vaccines against HPV types 16 and 18 is uncertain. Although all cervical cancer is caused by HPVs, types 16 and 18 (i.e. the vaccine types) account for only 65-70% of cases. An additional 13-16 HPV types cause the remaining 30-35% of cases. The proposed study will assess the impact of the HPV 16/18 vaccine on the other oncogenic HPV types. The primary hypothesis of the study is that the prevalence of vaccine and non-vaccine HPV types will change as a result of vaccination against types 16 and 18. If confirmed, this would indicate that the incidence of cervical cancer from non-vaccine HPV types will change in the wake of vaccination. Considering the staggering global burden of cervical cancer, understanding how this new preventive intervention impacts the disease is a critical public health concern. The proposed study will be carried out as a sub-study within a larger European-funded project in South Africa. The three specific aims of the proposed project are: 1) To assess the impact of the quadrivalent HPV vaccine on the distribution of non-vaccine HR-HPV in the study population, 2) To determine and compare the pre- and post-vaccination distribution of HR-HPV among HIV-infected and HIV-uninfected sexually active young women in South Africa, and 3) To analyze the association of cervical dysplasia with the results of HPV DNA analysis in the study population. The fundamental design of the proposed project is a longitudinal cohort study in which sexually active young women will be tested for HPV DNA, vaccinated, and then re-tested for HPV at six month intervals. The HIV positive subgroup within our study population will receive special focus as this widely prevalent co-morbidity may effect HPV distribution and vaccine response. Pap smears of all study participants will be performed upon study enrolment and exit to enable correlation of HPV infection with cervical disease. The candidate's career goals include becoming an established, independent investigator of infectious disease prevention in the developing world. Executing the proposed project will prepare the candidate to accomplish this goal. PUBLIC HEALTH RELEVANCE: Project Narrative/Relevance Understanding how vaccination against some types of cancer-causing HPVs affects the distribution of the many other types of cancer-causing HPVs is essential to anticipating the impact of vaccination on reducing cervical cancer. During the development of the next generation of HPV vaccines, knowledge gained from the proposed project will directly address the question, Vaccination against which HPV types will save the most women's lives?.